Contribution of 4-1BBL on radioresistant cells in providing survival signals through 4-1BB expressed on CD8(+) memory T cells in the bone marrow.

MedLine Citation:

PMID:
22886791
Owner:
NLM
Status:
Publisher

Abstract/OtherAbstract:

The persistence of memory lymphocytes is a critical feature of adaptive immunity. The TNF family ligand 4-1BBL supports the antigen-independent survival of CD8(+) memory T cells. Here we show that mice lacking 4-1BB only on αβ T cells show a similar defect in CD8(+) T-cell recall responses, as previously shown in 4-1BBL deficient mice. We show that 4-1BB is selectively expressed on bone marrow CD8(+) but not CD4(+) memory T cells of unimmunized mice. Its ligand, 4-1BBL, is found on VCAM-1(+) stromal cells, CD11c(+) cells and a Gr1(lo) myeloid population in unimmunized mice. Adoptive transfer of in vitro-generated memory T cells into mice lacking 4-1BBL only on radioresistant cells recapitulates the defect in CD8(+) T-cell survival seen in the complete knockout mice, with smaller effects of 4-1BBL on hematopoietic cells. In bone marrow, adoptively transferred DsRed CD8(+) memory T cells are most often found in proximity to VCAM-1(+) cells or Gr1(+) cells, followed by B220(+) cells and to a much lesser extent near CD11c(+) cells. Thus a VCAM-1(+) CD45(-) stromal cell is a plausible candidate for the radioresistant cell that provides 4-1BBL to CD8(+) memory T cells in the bone marrow.